The rheumatologist's decision on whether or not to learn about complementary therapies has become more complex as patient use has become more widespread. Americans spend more on such therapies for osteoarthritis than for any other medical condition. Thus, every physician should be aware of what patients are taking for safety reasons. Further, it is important that they be aware of substances that might be dangerous to their patients, and caution patients about their use.
Any dietary supplement or herb may potentially interact with other medications the patient is taking or might take at a time of crisis, such as trauma or surgery. Because some patients do not tell their physicians about use of these products for fear of disapproval, it is important that physicians ask about use of complementary therapies in a non-judgmental manner and document such usage for future reference when other drugs are prescribed or surgery is scheduled.
This report reviews research on agents most commonly used by arthritis patients: glucosamine, chondroitin, SAM-e, ginger, boswellia, DMSO, MSM, turmeric, guaifenesin, and vitamins C and E.
Glucosamine sulfate has been shown to provide modest pain relief for osteoarthritis (OA) of the knee. Small randomized controlled trials, as well as a meta-analysis suggest glucosamine sulfate might be an effective treatment for OA in reducing pain and improving function. A large prospective multi-center trial, supported by the National Institute of Health, is currently underway. With regard to chondroprotection, one recent study of 212 patients showed that glucosamine sulfate delayed progression of mild to moderate knee OA compared to placebo. More studies are needed for definitive answers.
Glucosamine often is sold in combination with chondroitin sulfate (discussed below); however, to date no study has shown the combination to be more efficacious than glucosamine alone. The NIH study will examine the efficacy of the combination of glucosamine and chondroitin sulfate, as well as each agent alone.
Possible side effects include nausea, diarrhea, heartburn, drowsiness, skin rash, and headache. A recent randomized, placebo-controlled trial did not find that glucosamine raised blood glucose levels within the 90 day study period. There has been concern that glucosamine derived from marine exoskeletons may cause reactions in people allergic to shellfish;, however, we have not found documentation of such reactions. There is insufficient data about possible interactions with herbs and other supplements.
Glucosamine sulfate 1500 mg qd for patients with pain due to OA may be considered. Response is slower than with NSAIDs. However, if glucosamine has not proved helpful after 3 months of use, recommend discontinuing it. Preparations are not standardized. Independent testing done to determine whether products contained the labeled amounts of glucosamine found that nearly one-third of products did not pass testing.
Chondroitin sulfate has been shown to provide modest pain relief from OA of the knee. One randomized controlled trial found improvement in pain and function in 63 patients with knee OA treated with chondroitin sulfate 1000 mg daily. However, in the intention-to-treat analysis, this improvement was non-significant compared to placebo. Another randomized controlled trial compared chondroitin sulfate 400 mg tid to diclofenac sodium 50 mg tid, with improvement in pain in both groups. The chondroitin sulfate treated patients had a therapeutic response that was slower and longer lasting, up to 3 months after treatment completion, compared to the diclofenac group. An efficacy and tolerability study compared chondroitin sulfate 1200 mg daily versus chondroitin sulfate 400 mg tid. This was also a randomized, placebo-controlled trial. There was a significant improvement in pain in the chondroitin sulfate treated groups compared to placebo. Efficacy between the single daily dose of 1200mg did not appear to differ from that of 400 mg given tid. Treatments were well tolerated.
Several small randomized controlled trials,, have examined the combination of glucosamine and chondroitin sulfate for OA of the knee and/or low back. These studies varied in their inclusion of intravenous glucosamine, glucosamine hydrochloride, and manganese ascorbate. In general, chondroitin sulfate combined with these other agents was found to improve symptoms of OA compared to placebo.
Side effects of chondroitin sulfate may include upset stomach, nausea, diarrhea, constipation, edema and alopecia. There are no known drug interactions. Again, there is insufficient data on possible drug interactions.
Chondroitin sulfate may be considered - up to 1200 mg daily or 400 mg tid for the treatment of pain from OA of the knee. Response is slower than with NSAIDs. However, if chondroitin has not proved helpful after 3 months of use, recommend discontinuing it. The same precautions about lack of standardization as with glucosamine (above) apply.
SAM-e has been shown to provide equal or greater pain relief for OA compared to traditional non-steroidal anti-inflammatory drugs (NSAIDS). Several small studies,, comparing SAM-e with various NSAIDS (ibuprofen, indomethacin and piroxicam) showed comparable improvements in pain and function for OA of the knee, hip and/or spine. The dosage of SAM-e used was 1200 mg qd. A larger, long-term open trial studied 108 patients with OA of the knee, hip and spine, using 600 mg qd of SAM-e for two weeks followed by 400 mg qd to complete two years of treatment. Pain and stiffness improved, starting after the first week of treatment and continued to the end of the 2 year period.
A meta-analysis of 7 randomized controlled trials comparing SAM-e to NSAIDS or placebo for OA did not find enough evidence for efficacy of either SAM-e or oxaceprol. There may be comparable effect of SAM-e to other NSAIDS.
SAM-e can cause flatulence, vomiting, diarrhea, headache and, in depressed patients, anxiety. Adverse effects are dose related. Concurrent use with antidepressive agents may cause serotonin syndrome-like effects such as tremors, tachycardia, tachypnea, diarrhea and hyperreflexia. Gastrointestinal side effects may be reduced by taking enteric-coated tablets, taking it with meals, or reducing the dosage. There is insufficient information about interactions with other supplements.
SAM-e may be considered - 200 mg to 400 mg tid for treatment of pain in patients with OA may be considered. SAM-e is started at a dose of 200 - 400 mg on the first day and increased gradually. Improvement of symptoms can occur within a few days to 4 to 5 weeks. The labeled amount of SAM-e in available products generally range from 100 mg - 200 mg. However, independent testing to determine whether products contained the labeled amounts found that 6 out of 13 SAM-e products did not pass testing standards.
Promising but insufficient evidence supports the use of ginger for OA, and there are potentially side effects and drug interactions . A randomized, placebo-controlled trial comparing ginger extract to placebo and ibuprofen did not find significant difference between ginger and placebo for OA of the hip or knee. Another randomized controlled trial compared ginger to placebo for knee OA in 261 patients and showed moderate improvement in symptoms. There was no difference in quality of life between the two groups, and the ginger treated subjects had more gastrointestinal side effects compared to placebo.
A small, uncontrolled study of patients with musculoskeletal pain (rheumatoid arthritis, OA, and muscular pain) treated them with powdered ginger for up to 3 years. More than 75% of the arthritis patients had improvement in pain and swelling, without report of side effects. Ginger oil has been shown to improve joint swelling in adjuvant arthritis rat models.
Ginger root, fresh or dried, is taken orally. Possible side effects include dyspepsia and, in large doses, ginger may cause central nervous system depression and cardiac arrhythmias. Possible interactions with drugs and herbs with anticoagulant/antiplatelet properties could increase the risk of bleeding. Such drugs and herbs include NSAIDS, warfarin, garlic, gingko, ginseng, feverfew and turmeric.
Do not recommend ginger for treating arthritis.
Although one prospective, controlled study supports the use of topical DMSO for arthritis, considerable cautions apply to this substance. The study was done with a mixed population of RA, OA and JRA patients and showed that a cream with DMSO may offer subjective improvement in joint symptoms. There are no other prospective controlled studies of DMSO for OA.
Other data are equivocal. A blinded, controlled study evaluated DMSO cream in 102 patients with lateral epicondylitis or rotator cuff tendinitis, with improvement in pain, swelling and range of motion. However, patients treated with the 70% DMSO aqueous solution did not receive any more benefit than patients who received the 5% DMSO aqueous placebo solution.
DMSO is an industrial solvent, and the products sold in the market may not be pure or properly mixed. Thus, it can carry any number of toxins through the skin. Because products are not standardized, dose is unknown. Topical usage may cause dermatitis, and systemic use may be associated with renal, hepatic and opthalmologic side effects.
Do not recommend topical over-the-counter DMSO for treating arthritis, particularly as there are potential hazards. Advise patients not to use it because of potential impurities that can be carried through the skin. Variations in product quality may occur.
MSM is a sulfur compound derived from the breakdown of DMSO. It can be found in certain algae species, fruits, vegetables, milk, fish and grains. Despite its popularity, no randomized controlled trials have been published in the peer-reviewed literature to support use of this agent. Animal studies suggest MSM and DMSO may help decrease inflammatory joint disease.
Side effects of MSM may include nausea, diarrhea and headache. There are no known interactions with other supplements or drugs, although data are limited.
Do not recommend MSM at this time. Given the lack of data in humans, there is no basis for its use.
MSM is available in doses of 1000 to 3000 mg. It is frequently sold in combination with other products such as glucosamine and chondroitin sulfate. However, if patients are using glucosamine and/or chondroitin, they should be advised to select products with those agents alone and avoid MSM, which has no proven benefit and may increase their risk of side effects.
There is insufficient evidence to support the use of turmeric for osteoarthritic pain. A turmeric extract was used to treat OA in dogs in a double-blind, placebo-controlled trial. There was no significant difference between the treatment and placebo groups. A turmeric extract and curcumin ointment was tested in 62 patients with external cancerous lesions in an uncontrolled study. There was a reduction in lesion size and pain in10% of the patients. Oral administration of capsaicin and turmeric lowered the levels of paw inflammation in adjuvant arthritis in rats, as well serum levels of an acidic glycoprotein.
Potential side effects include GI upset. Contraindications include patients with peptic ulcer disease, bile duct obstruction and gallstones. Possible interactions with drugs and herbs with anticoagulant/antiplatelet properties could increase the risk of bleeding.
Do not recommend turmeric for treating arthritis. Despite the fact that it is widely promoted in the alternative literature, its benefits are anecdotal and more research is needed.
Preliminary but incomplete data suggest that boswellia serrata, in combination with other herbs, may improve pain and function in patients with OA. Boswellia is an Asian tree also called salai guggal or Indian frankincense. Boswellia inhibits leukotriene synthesis in vitro by inhibiting 5-lipoxygenase activity both in rat neutrophils and human platelets.
A single-blinded, placebo-controlled randomized controlled trial found improvement in pain and disability in OA from a formula containing boswellia, withania, curcuma and a zinc complex. Several randomized controlled trials have assessed the effect of multiple plant-based formulations, including boswellia, in rheumatoid arthritis. One showed significant improvement, and one did not. No prospective, clinical studies on boswellia as a single agent have been done on OA patients. However, boswellia has been a commonly used anti-inflammatory agent for arthritis, asthma and ulcerative colitis in Ayurvedic medicine.
Boswellia does not appear to have any major side effects necessitating withdrawal from these studies, but may cause minor gastrointestinal disturbances or rash. There are no known interactions with other drugs.
Do not recommend boswellia serrata at this time, and patients should be cautioned about problems in formulations. Standardization of products may be problematic, and some Ayurvedic formulations have been found to have steroids and NSAIDS mixed in. Boswellia may be sold as a standardized extract of the gum oleoresin and the usual dosage is 150 mg tid for 2-3 months. It also comes in combination products.
Guaifenesin has been used as an anesthesia in veterinary medicine in conjunction with other anesthesics,. In humans, it is used as an expectorant in over the counter medications. There is no evidence to support the use of guaifenesin for fibromyalgia or any other pain condition in humans. The National Fibroyalgia Research Association funded a study in 40 women with fibromyalgia who were given either 600 mg of guaifenesin or placebo bid for one year. No improvements were found in muscle aches, grip strength, quality of life or walking speed compared to placebo.
Side effects of guaifenesin include nausea and vomiting. Due to interactions, guaifenesin should not be used in combination with MAO inhibitors.
Do not recommend guaifenesin for fibromyalgia.
Preliminary but incomplete data suggest considering the use of vitamin C in the treatment of OA, but animal studies show potential problems with high doses. Taking vitamin C may be associated with reduced risk of cartilage loss and knee pain, but no randomized controlled trials have been done. A longitudinal study showed that patients taking high dose vitamin C had a reduced risk of knee cartilage loss and knee pain. However, an animal study showed that guinea pigs maintained on high doses of vitamin C had severe joint damage compared to animals on low doses of vitamin.
Side effects of vitamin C include nausea, vomiting, heartburn, abdominal cramps, fatigue, flushing, headache, hyperoxaluria and precipitation of renal stones. Interactions associated with vitamin C include increased oral iron absorption, and when used with salicylates, decreased excretion of salicylates.
Do not recommend vitamin C for the treatment of OA.
There is preliminary but incomplete and conflicting data to support the use of vitamin E in the treatment of knee OA. A longitudinal study showed that patients taking vitamin E were found to have a reduced risk of progression of knee OA36. However, a small randomized controlled trial of 77 patients with knee OA showed no benefit for the management of symptomatic knee OA compared to placebo.
Side effects with vitamin E are rare but may include nausea, abdominal cramps, headache, rash, and, at high dose, increased risk of bleeding due to antagonism of vitamin K-dependent clotting factors and platelet aggregation. When used with anticoagulant and antiplatelet drugs and herbs (i.e., angelica, capsicum, chamomile, feverfew, garlic, ginger, ginkgo, ginseng, red clover and turmeric), vitamin E may increase the risk of bleeding.
Do not recommend vitamin E for the treatment of OA.
When discussing supplements with patients, it is important to emphasize that they are not regulated by the Food and Drug Administration in the same way that prescription drugs are. Therefore, no agency is supervising the manufacturers to assure that the products actually contain what is on the label. Consumers should avoid brands that use words like "cure" or "miracle treatment." When purchasing herbs, look for products whose labels include the product name, Latin name of the plant, part of the plant that is used, amount in each dose, a claim or statement of nutritional support, and an FDA disclaimer.
The physician needs to be knowledgeable about, or have access to, authoritative sources for information about herbals and other supplements. For both physicians and patients, it's wise to use non-industry sources to learn more about complementary therapies.
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